PAUL MICHAEL SCOLA,ERIC MULL,MARTIN PATRICK ALLEN,MICHAEL MATTHEW MILLER,ERIC P. GILLIS,QIAN ZHAO,LI-QIANG SUN
申请号：
ARP150104203
公开号：
AR103182A1
申请日:
2015.12.18
申请国别(地区):
AR
年份:
2017
代理人:
摘要：
It provides macrocyclic peptides that inhibit the interaction of protein / protein ppd-1 / PD-L1 and PD-L1 / CD80, thus contributing to the improvement of various diseases including cancer and infectious diseases. Requirement 1: a compound having the properties of formula (1),Or a pharmaceutically acceptable salt, wherein: A is selected from the link, or a formula group compound (2)；Corrugated line * indicates the connection point with carbide group, corrugated line indicates the connection point with nitrogen atom； Z is 0, 1 or 2； W is 1 or 2； n is 0 or 1； m is 1 or 2； m is 0 or 1； P is 0, 1 or 2； r739 selects hydrogen, amine, hydrogen Xi and methyl； R183088 and r183099 are independent of hydrogen and methyl； r761111 is selected from hydrogen y-c (o) nhr18310；Where r8310 is selected from the hydrogen gas, - chr18311； (o) nh8322；-CHR¹⁷C (O) NHCHR¹⁸C (O) NH₂ and -CHR¹⁷C (O) NHCHR¹⁸C (O) NHCH₂C (O) NH₂；e. Rr831111 selects hydrogen and - ch83228oh, and r1831222 selects hydrogen and methyl； r7515 is a side chain of hydrogen or natural amino acids； r758080；R75848,R688a,R83055 and r75040 are hydrogen； r83199 is hydrogen or methyl, or r7515 and r83199 form a pyridine ring； r7491；R74977,Rʲ and Rᵏ are independently selected from hydrogen and methyl； each R²⁰ is independently selected from hydrogen and C₁₋₆alkyl； each R²¹ is independently selected from hydrogen and C₁₋₆alkyl； R¹,R2,R3,R830808,R83099,R8310,R8311th,R8322,R8313,R830404,R1,R¹² and R¹³ are independently selected from a natural amino acid side chain and an unnatural amino acid side chain, or each can independently form a three to six membered carbocyclic ring or a six member ring containing an oxygen or oxygen atom. nitrogen with a corresponding germinal R²⁰ group, wherein the ring is optionally substituted with one, two or three substituents independently selected from C₁₋₃alkoxy, C₁₋₃alkyl, C₂₋₄alkenyl, halo, hydroxy and amino and where the ring of five and six members are optionally fused to a phenyl ring； or R¹
